JPS63501139A - Magnetic flux switching flow chamber for high-gradient magnetic separation of particles from liquid media - Google Patents

Abstract

A system for the magnetic separation of fragile particles, such as intact biological cells, from a fluid medium. The system includes at least one high-gradient magnetic separator having a flow chamber housing an interstitial separation matrix and associated magnetizing apparatus for coupling magnetic flux to the matrix. The matrix has interstices through which a carrier fluid carrying the cells-to-be-separated may be passed. The magnetizing apparatus includes opposing North and South poles and field-guiding pole pieces, external to the flow chamber. The flow chamber comprises a dual-position flux-coupler. The flux-coupler is operative in a first position in the capture phase and in a second position in an elutriation phase. In the capture phase, the flux-coupler is positioned to permit the magnetic flux from one magnetic pole to pass through the matrix to the other magnetic pole. As the carrier fluid flows through the interstices of the matrix in this phase, particles, such as blood cells, in the input fluid are retained in the matrix, where magnetic forces dominate gravitational and viscous forces. In the elutriation phase, the flux-coupler is positioned so that magnetic flux is diverted from the matrix. In this phase, magnetic flux is greatly reduced in the matrix, permitting viscous forces to the fluid to remove the magnetic particles from the matrix at low flow velocities.

Description

[Detailed description of the invention] High-gradient magnetic separation of particles from liquid media Magnetic flux conversion flow chamber for separation [Related applications] The subject matter of this application is "Particles from a Magnetic Separation Matrix," which was filed concurrently with this application. Related to the subject matter of U.S. patent application Ser. do.

[Background of the invention] The present invention relates to the field of instruments, and in particular to magnetically separating particles 1 from a liquid medium. It relates to a device for.

Magnetic separation of a solid substance from a fluid medium has been described in the prior art by The process has been carried out without regard to the integrity of the process. For example, mineral slurry Processes for separating iron oxides from iron oxides are well known. In fact, these separations The treatment involves the use of harsh chemicals between the separated particles and between the separated particles and the separation matrix. resulting in harsh physical interactions. Generally, in this field of magnetic separation, Although there is often a concern about maintaining the integrity of the trix, There is no need to worry about the integrity of the particles.

In other applications of magnetic separation, the integrity of the separated particles is important. example For example, to separate living biological cells from a fluid carrier, these cells must be It is necessary to isolate intact cells so that they can be analyzed. Another example is It is desirable to separate aggregates of particles from the carrier fluid while maintaining their cohesive relationship. can be thought of as "particles" that are Well-known separation techniques useful in these areas are , high gradient magnetic component*HGM a method.

In the conventional HGM8 device, particle collection is carried out by magnetic wires placed in the magnetic flux , on a matrix of fibers, spheres or other high permeability materials.

This type of matrix generally has pore spaces through which the particles and carrier fluid can pass. It is characterized by containing. As the particles pass through the matrix, each particle Receives a magnetic force proportional to (ψ, −ψ1)vpHdH/dX toward the lix element . Here, ψ is the magnetic susceptibility of the particle, ψ is the magnetic susceptibility of the carrier fluid, and vp is the magnetic susceptibility of the particle. The volume, ■ is the magnetic field strength, and X is the spatial dimension from the matrix surface. ψ, is ψ , i.e. in positive magnetic mode of operation where the particles are also ``magnetic'' than the carrier fluid. In the magnetic field, particles are attracted to the matrix elements in the “strong magnetic field” region. . On the other hand, ψ.

exceeds ψp, that is, when the carrier fluid is like a particle, there is also a magnetic J In this mode, particles are repelled from regions of strong magnetic field, but are repelled from regions of weak or low magnetic field. is attracted to the matrix element〇 During the capture operation phase, the fluid carrying the particles to be separated is The flow is low enough that the magnetic attraction force on the particles exceeds the viscous and gravitational forces. pass through the matrix in quantity. As a result, these particles The carrier fluid exits the matrix while being retained or captured. Next, the washing step Initiating the step and collecting captured particles from the matrix for e.g. post-squeezing analysis Can be done.

Magnetic flux is generated by an electromagnet or a permanent magnet, and the magnetic flux is used during the cleaning and separation (washing out) stage. In HGM8 rice, which is removed from the matrix by some means, the grains After collecting particles from the particle load carrier, the device first applies a drive voltage to the windings of the 'IIL magnet. by interrupting the flow or by removing the permanent magnet flux from the matrix. Toyoshi is released from the Matrix. However, due to residual magnetism within the device, Therefore, some particles may be retained in the matrix. At that time, the cleaning fluid The velocity at which the tube is driven in the matrix removes unreleased particles from the matrix. selectively increased.

H in which the magnetic flux is generated by a permanent magnet and the matrix is always maintained in the magnetic flux path. In a GMS device, the magnetic flux retains trapped particles even with the introduction of a washing fluid. I sometimes get angry. General methods for cleaning and detaching trapped particles in this case is to increase the fluid flow rate so much that the viscous drag exceeds the magnetic coercive force. ◇In this way, the captured particles are washed away from the matrix. child The latter method has been widely used with inorganic particles, but it has been used extensively with intact living biological cells. It has been less successful when applied to the separation of fragile particles such as especially old blood When the fluid undergoes this method of cell washing, the cell debris observed in the wash effluent is This method has been shown to be too harsh for use in many clinical samples.

It is therefore an object of the present invention to provide an improved method for magnetically removing particles from fluid media. The objective is to provide a device that has improved performance.

A particular object of the present invention is to magnetically capture fragile particles within a fluid medium and then remove them intact. An object of the present invention is to provide an improved device for the removal of .

Another particular object of the invention is to magnetically capture intact biological cells from a fluid medium and to The object of the present invention is to provide an improved device that allows its removal from the environment.

[Summary of the invention] The present invention magnetically separates fragile particles, such as intact biological M vacuoles, from a fluid medium. It's all about technology.

Specifically, the present invention provides a flow chamber containing a porous separation matrix; a high gradient magnetic component with an associated magnetization device for coupling magnetic flux to the matrix; Provides separation (80M8) equipment. The porosity matrix provides high permeability rear, a carrier fluid, which may be a fiber, sphere or the like, carrying the cells to be separated; It has a thin @ that can pass through. The magnetizing device has opposing N poles and It comprises a permanent magnet with 8 poles and a magnetic field guiding pole piece. The flow chamber has dual position magnetic flux Equipped with a coupler.

The flux coupler operates in the first position during the capture phase and in the second position during the scour phase. can be made.

During the capture phase, the flux coupler allows the magnetic flux exiting the -magnetic pole to pass through the matrix. It is positioned so that it can pass through to the other magnetic pole. At this stage, the carrier As fluid flows through the pores of the matrix, magnetic attraction forces overcome viscous and gravitational forces. Input fluid particles (such as blood cells) that generate blood are retained within the matrix.

During the washing phase, the magnetic flux cup 2 is arranged such that the magnetic flux is diverted from the matrix. It is positioned as At this stage, the magnetic flux is significantly reduced from the matrix. The viscous forces of the fluid capture it from the matrix at low flow velocities. It becomes possible to remove the trapped particles. HG of the type taught by the present invention The MS device non-destructively separates fragile particles such as intact blood and iocytes from a carrier fluid. can be released.

According to another aspect of the invention, an acoustic ablation device is integrated into the flux-directing flow chamber and It assists in releasing the trapped particles from the matrix during the desorption step. acoustic The removal device includes a piezoelectric transducer coupled to the matrix and an associated A drive circuit is provided. As an example, a piezoelectric transducer can be fixed to the wall of the chamber housing the matrix in fluid communication; good. Instead, EEt! ) The thin juicer is mechanically coupled to the matrix. It's fine.

According to this aspect of the invention, during the capture phase, the HGM8 device is in the first position. It operates with some flux couplers and in other cases in the conventional manner, with fragile particles being magnetically selectively captured from the carrier fluid passing through the It may be possible to ensure that the captured particles are held in place within the matrix.

During the washout phase, a flux coupler is installed so that the magnetic flux is diverted from the matrix. The body is placed in a second position and a wash flow is passed through the matrix. Minimum wash rate For applications where this is essential, a drive circuit excites the piezoelectric transducer. Transdi The user responds to this excitation by setting an acoustic wave in the cleaning fluid passing through the matrix. Fixed! Make Trix itself vibrate. Acoustic waves are generated by mechanical impeders in the flow chamber. Ultrasonic waves may be used depending on the situation. Acoustic waves and matrix vibrations stimulate intact cells. When using the magnetic flux diversion feature of the present invention, This also allows for a sufficiently low washout flow fit as may be required.

In various embodiments of the invention, a single separator tube may be used (alternatively) Separator tubes mechanically coupled to the separator tube may be arranged in a double separator configuration.

[Brief explanation of the drawing]

These and other objects and various features of the present invention will be understood with reference to the drawings. It will become clear from the explanation below.

FIG. 1 is a perspective view of a separation device constructed in accordance with the present invention.

2 and 3 are vertical cross-sectional views of the separator of FIG. 1; FIG.

Figures 4 and 5 are horizontal sectional views of the separator shown in Figure 1. Figures 6-11 show embodiments of the double separator of the present invention.

FIG. 12 is a cross-sectional view of the double separator embodiment of FIG. 6;

FIG. 13 shows an alternative double separator embodiment of the present invention.

[Description of preferred embodiments]

Figures 1-5 show a separator 10 for a high gradient magnetic separation (80M8) device. This fruit The separator 10 of the embodiment includes a permanent magnet for generating a magnetic field used for particle separation. ing. The present invention can also be applied to an electromagnetic HGMf9 device, but in this case, for separation The magnetic field is generated by an electromagnet, and removal of trapped particles is achieved by energizing or de-energizing the magnet. It can be achieved either way.

The separator 10 extends along a reference axis 13 and includes an inlet 14 and an end member 14'. and an outlet 16 and an end member 16'! A cylindrical flow chamber 12 is provided.

In other embodiments of the invention, additional inlets and outlets may be provided to the flow chamber 12. It may be provided. In the embodiment disclosed herein, axis 13 is aligned with the local vertical. has been done.

The chamber 12 is configured such that fluid flow entering the inlet 14 flows along a flow axis 17 to the outlet 16. It is configured so that it can be used. Outside the chamber 12 is a permanent magnet assembly. is provided. The magnet assembly has a north pole 18 and its associated high permeability magnetic field. A focusing pole piece 20 and a south pole 22 and associated high permeability magnetic field focusing pole piece 24 are provided. I can do it. Pole pieces 20 and 24 together with flow chamber 12 provide magnetic flux between magnetic poles 18 and 22. Set the route. In the case of a permanent magnet embodiment, poles 18 and 22 are a single "horseshoe" or C-shaped magnets. In the case of electromagnet embodiments, the conventional type 'tlL magnets and energizing circuits (not shown) may be used. On the end member, A reference line 26 passing through axis 13 and axis 17 is shown. This reference line 26 is In the drawings, the angular orientation of the turns of the axis 13 of the chamber 12 is indicated.

As shown in the cross-sectional views of FIGS. Contains xsad. Matrix 30 drives between inlet 14 and outlet 16. within the flow chamber 12 in such a manner that the fluid to be moved passes substantially through the matrix 30. It is positioned along axis M17. ! Trix 50 is a carrier fluid and a magnetic wire, fiber, having a mat-sized material large enough to allow the passage of particles; A conventional type of high permeability assembly consisting of a sphere or the like. As an example, The matrix element may be 5-15% of the internal volume of the chamber.

As shown in FIGS. 1 to 5, within the matrix so, the flow axis 17 is Semi-axis! ! 13, and in this example the local vertical machine and alignment They are lined up. In other embodiments of the invention, any angle between 0 and 90 degrees may be used. may be tilted from vertical. The inclination of axis 17 is optimally approximately equal to 45 degrees. Good. However, other orientations can also be used. In an exemplary embodiment where the inlet 14 is lower than the outlet 16, In embodiments, the fluid flow in chamber 12 is directed against the local gravitational field. As a result, the gravitational field favors the particle flow within the carrier fluid. In a preferred embodiment, the chamber 12 has a cylindrical side that is non-magnetic, ie has a low magnetic permeability. It is formed from wall members 4o and 42 and magnetic cylindrical side wall members 44 and 46. It will be done. The outer surfaces of members 40, 42, 44 and 46 are cylindrical coaxial with reference axis 15. form a shaped surface. Is the entire flow chamber 12 selectively rotatable in the direction of the fine pole 13? In the first position shown in FIGS. 1, 2, and 4, from the magnetic pole 18 to the pole Piece 20, side wall member 44, matrix 30, side wall member 46 and pole piece 24 A magnetic flux path is established leading to the pole piece 22. Chamber 12 is shown in FIGS. In the second position of the chamber 12, which is rotated 9 CP with respect to the first position, the magnetic From the pole 18 to the pole piece 20, through the side wall members 44 and 46 and the pole piece 24, the magnetic pole Since a low reluctance path is established leading to 22, the magnetic flux substantially passes through the matrix 50. take a detour. The main magnetic flux paths for the two positions of chamber 120 are shown in FIGS. 4 and 5, respectively. Indicated by arrows in the figure. In an exemplary embodiment, the main body illustrated in FIG. The magnetic reluctance of the magnetic flux path is considerably higher than that of the main magnetic flux path illustrated in FIG. .

In one embodiment, although not required for all embodiments of the invention, the piezoelectric plate 52 (e.g., wall 40). Board 52 is a drive circuit 53. As is well known in the art of ultrasonic transducers, a piezoelectric plate 52 A back load member 54 is used for one-wavelength impedance matching of the load to the Good morning. In the illustrated embodiment, the plate 52 is mounted on the side wall plate 40 of the chamber 12. It is mounted electrically insulated from the side wall and mechanically connected to the matrix 30. being contacted.

In other embodiments of the invention, plate 52 may be spaced apart from 50 (but ). Plate 52 holds the fluid containing the particles to be separated. It may be placed directly on the surface of the building or separated from it by a thin film, insulating film or the like. good.

A preferred embodiment is to extract intact biological cells (red blood cells) from a fluid medium (such as whole blood). etc.). In this embodiment, the capture operation stage For driving the fluid medium into the chamber 12 at the floor, a fluid drive device or pump is provided. It is provided. During this capture phase, chamber 12 is placed in the position illustrated in Figures 1.2 and 4. In this case, the plate 52 is passive and the magnetic field passes through the matrix 30. Mato Cells passing in close proximity to the lix elements are Similar to the magnetic field, the forces generated on these particles affect these elements. to be kept or captured.

When the loading capacity of the matrix 30 is reached, the supply fluid is replaced by the cleaning fluid and the cleaning The withdrawal phase will begin. During this stage, the ¥12 is shown in Figures 3 and 5. position, so that the magnetic field is transmitted through side wall members 44 and 46, i.e. It is shunted to the return of Rix 30.

In order to wash and detach the captured particles from the matrix 30, a magnetizing magnetic field is applied. Even in the presence of a relatively low fL flow rate compared to that required by the prior art. The quantity is sufficient.

Optionally, in exemplary embodiments that include piezoelectric plate 52, even lower washout To enable the flow rate to be used, drive circuit 55 drives plate 52 to provide a high flow rate. For example, a sound with a frequency of 15) Hz iw'tf! i, is generated in the fluid in the chamber 12. Ru. The drive waveform generated from the circuit 55 is, for example, a pulse from an energy storage circuit. Or it can be a pulse train. Alternatively, the driving waveform is designed so that the captured particles are washed away. It may be a periodic oscillation that is gated off after the signal is applied, or any other suitable waveform. use Regardless of the specific drive waveform used, the sound set by the plate in response to the drive. The acoustic wave is an acoustic wave that mechanically drives the matrix 30 or propagates through the room space. The action releases particles from the matrix; as a result, the captured particles become magnetically Difficulties that can be tolerated only by bundle turning can also be removed with a low flow hammer. Reduced flow rate during outbreaks The amount of the member 54 on the outer surface of the plate 52 varies depending on the intensity of the sound wave. It becomes more effective depending on the back load set by the model.

Thus, according to the invention (with or without plate 52), magnetic poles 18 and and 22, pole pieces 20 and 24, and flow chamber 12 on its axis @ 130 turns. (by mechanical rotation), the magnetic flux for magnetization is diverted to the matrix 300 times. Form a magnetic switch. In the illustrated embodiment, matrix 30 includes chambers 12 Although shown as being in direct contact with the paulownia structure of chamber 120, alternatively, chamber 120 contained within a suitable, even disposable, cartridge that can be inserted into the rotating cooperage. You can also let Pole pieces 20 and 24 and side members 44 and 46 may be mild steel. . Alternatively, other highly saturable substances may be used. Corrosive carrier fluid is present on m wall 4 4 and 46, these parts are made of magnetic stainless steel. It will be considered as Pole face geometry 11-complete, with short magnetic fields in the chamber and matrix. In order to define the air gap, these magnetic pieces are placed over the entire matrix body. setting the desired magnetic field, thereby allowing effective capture of the particles to be separated. I can do it.

When chamber 12 is in its second position, i.e. during flow, magnetic pieces 44 and 46 are , zero piece/pole piece that effectively shunts the magnetic gap and diverts the magnetizing flux into the piece. The minimum cross-sectional area of the structure satisfies the piece material at the selected magnetizing field strength. If the sum area is large, then the residual magnetic flux in the 9x30 exists during the capture stage. It is greatly reduced compared to the level. At that time, the captured particles will be reduced accordingly. The chamber can be washed away at a flow rate of can be returned to position.

In other embodiments, a sample may include a cylindrical section (such as section 44 or 46). A sampling chamber t'' is provided on one side, and this is filled during the dissemination phase of the preceding cycle. It can be diluted. during the next capture stage, those in this sampling chamber. The matrix 30't is flushed into the chamber containing the matrix. It will be done. In one form of blood cell separation, this 7 latching is performed using reducing agents or acids. This may be accomplished with a suitable fluid, such as isotonic saline containing a curing agent.

In accordance with the present invention, the flowing fluid velocity reduces the magnetizing field strength within the matrix 30. The fluid shear forces and mass applied to multiple cells can be reduced proportionally to Trix collision forces can be reduced and cell fragmentation can be reduced. This is blood Particularly important when separation of red blood cells from whole blood is done to facilitate platelet counting It is.

In this case, fragmentation must be kept as small as possible for at least two reasons. do not have. That is, (1) each destroyed cell may produce several fragments; fragments are within the size range of true platelets. (2) Such a fragment has a matrix 1 & Optimized original blood cells are smaller, so they are captured with relatively low efficiency and true Appears in the effluent together with platelets. Also, some types of separable cells or particles If it is desired to separate particles or cells that are bound to Low dissemination power is essential since the body attached to it should appear in relation to it. .

One example configuration may include pole pieces 20 and 24 of tapered rectangular cross section. be. In this case, the pole pieces 20 and 24 are made of two non-magnetic stainless steel form a rigid assembly consisting of two opposed annealed copper pole pieces separated by a However, all the parts are silver-soldered together, and the rotating flow chamber 12f and the receiver are A through hole is drilled so that the In this exemplary configuration, the flow chamber 12 is in the flow position. A stop syringe is provided to prevent rotation.

If the chamber 12 is in the pole assembly, the straw is in the matrix body while in the capture position. α95Tf) generated a magnetic field. In contrast, when a room is in the rumor position, its master A magnetic field of α42T is generated within the Trix body, and when the chamber is removed, a magnetic field is created in the chamber hole. A magnetic field of α54T was generated ◇Further reduction in the magnetic field at the current position is due to the side wall 44 and 46 can be obtained by optimizing the cross-sectional area. indoor matrices The wire 50 is Al8I No. 430 wire with a diameter of 50 microns, bttb, chamber volume. It filled about 15% of the volume.

Using this configuration, the matrix 30 was magnetized to a LOT and -day old blood was collected for 10 m Diluted with isotonic saline containing the dithionite rIR salt of M. For the 3M acquisition stage, the room 12 is placed in the capture position, the applied voltage 'f of the plate 52 is set to 0, and the volume of the 5 filters is set to 0. This method is achieved by flushing in seconds, and compared to conventional HGMS. 'i pretended. Next, for three capture stages, chamber 12 is placed in the flow position and plate 52 is When the applied voltage is set to 0, the flow rate is about 2 filter volumes/sec, that is, the conventional flow rate. (by flushing at approximately 2 filter volumes/sec at 40% flow rate) The current theory has been carried out and the form of the present invention has been put to good use.

For both cases, using C0ULTERC0UNTR■mode/I/ZB From the data obtained, the average background-corrected separation efficiency was calculated. Traditional Data obtained from the operation showed a separation efficiency of 743%, with the flux turning chamber in the current position. The present data used in the present invention showed a separation efficiency of 816%. In addition, cell destruction C0ULTER■C along with the zB counter to determine if a breakdown has occurred. HNNELYLER ■Units) 1-Used. CHNNE for traditional style rumors The data obtained from the LYZER unit shows that there is no clear breakdown overlapping the normal platelet area. It was shown that there is a partial distribution. When the present invention is used, CHANNELYZBR Data from the unit shows much less distribution in this area. did. The data from the CHANNELYZER unit indicates the separation efficiency in the case of the present invention. is confirmed to be 5% higher. Fewer red blood cells are fragmented during the epidemic, so it is more common. It is thought that many will be captured. This removes red blood cells from the sample where platelet counts are intended. This is particularly advantageous if the The important thing is that during the capture stage This is because it is the ratio of platelets to red blood cells in the effluent. This ratio is the red blood cell capture This can be improved by improving red blood cell fragmentation and reducing platelet size.

6 to 12 show embodiments of the "double separator" of the present invention. In these figures In this case, two separations each similar to separation 010 described above in connection with FIGS. A device 10 is coaxially arranged along a shaft machine 15. Chambers 12A and 12B are (by a mechanical link indicated by dotted line 57). this link These chambers 12 and 12B are rotated by the actuator 59 on the axis 13. Ml 2A and 12Bvf-connected so that they can be selectively rotated as a unit. match. In FIGS. 6-12, members corresponding to similar members in FIGS. 1-5 are: Although identified by the same reference numerals, a suffix is added for separator 56A and The subscript B is attached to the container 56B.

In the embodiment of FIG. 6, the first magnetic circuit extends along the magnetic pole 18A and the polar axis 58A. and 22A, the second magnetic circuit connects magnetic poles 18B and 22A along polar axis source 58B. 2B). Magnetic poles 18A and 22A are magnetic poles 18B and 22A. Aligned with and superimposed on B, chamber 12A is angled at 90 degrees with respect to chamber 12B. It is rotated by the rotation of the axis 13. Figure 12 is a cross-sectional view of the configuration shown in Figure 6. In addition, poles 18A and 18B can be a single pole, and poles 22 and 22B may be a single magnetic pole.

In the configuration of FIGS. 6 and 12, one of chambers 12A and 12B is in its first position, or capture position, where the magnetic flux is directed from the associated magnetic pole through its matrix. when the other of chambers f2A and 12B is in its second or flow position. The magnetic flux from the associated magnetic pole is then shunted to the loops of that matrix.

In the case of the configurations shown in Figures 6 and 12, the room has 12 people and 12 people, except when changing positions. One of B is in its capture stage and the other is in its rumor stage. Orientation is switched When selected, the magnetic field assists in the switching. The reason is that one magnetic circuit When the magnetic reluctance between the poles of the path increases in a chamber being switched from its capture position, When the magnetic resistance between the poles of the other magnetic circuit is switched from its current position, This is because it decreases in the chamber where the Therefore, the configurations shown in FIGS. 6 and 12 are Compared to similar types of separator 10, it takes a small amount of power to switch between chambers 12A and 12B'i. It uses a relatively low power actuator 59 for switching. obtain.

FIG. 7 shows a dual separator configuration similar to that of FIG. Ta! shi, magnetic ai l 8A and 22A are 90 degrees from the magnets 18B and 22B to the rotation of the axis 15. After being rotated, chambers 12A and 12B are aligned with each other.

This configuration is functionally equivalent to the configuration of FIG. Here again, there are 12 people in the room and When one of chambers 12A and 12B is in the capture position, the other is in the flow position, and chambers 12A and 12B are in the capture position. 12B switching is assisted by a magnetic field. However, compared to similar single separators, Thus, only a relatively low power actuator 59 is required.

FIG. 8 shows a double separator configuration of foam. In this form, nine! a pair of Magnetic poles 18 and 22A are used with actuator 59. Room 12A is , rotated about the axis 13 by 90 degrees from the chamber 12B. In operation, chamber 12 When the person and 12B are rotated by the actuator 59), the rotation direction and axis Switching in the linear direction is assisted by a magnetic field, with chamber 12A having magnetic poles 18 and 22. B or chamber 12B is in its capture position in the magnetic field. while the other chamber is located outside the magnetic field. In this form, the comparison Only a low power actuator 59 is required. This is because the magnetic flux between the magnetic poles When the magnetic reluctance of the path increases at a certain wealth as it is being switched from its capture position, The magnetic resistance of the magnetic flux path in a certain chamber is changed from its current position. This is because the magnetic field assists in attracting the latter. This form has magnetic pole 18A and Figures 6 and 7 require only 1/2 of the magnetic flux for magnetization. This is particularly advantageous compared to the form of

In each of the configurations of FIGS. 6-8, separators 56 and 56B include one separator. so that the separator is always in its capture position] and the other separator operates in its current position. 1. It is best to operate independently. This simultaneous filtering and flushing in the separator pair Synthesis allows efficient operation at high throughput. The pull or split is subjected to the same conditions in the two separators 56A and 56B. may be subject to different conditions. For example, the two capture steps involve reagent and/or or the flow rate may be different, and the two flow stages may be different as well. In addition , in the configuration of FIG. 8, the two chambers t2A and 12B are are in their internal geometry, or their matrix 30 material, geometry. , may differ in size or filling factor. Furthermore, the shapes shown in Figures 6 and 7 In this case, two magnetic circuits may differ in their magnetization strength or other properties good. particle - separation of particles or cells from those similar in many of their properties A variety of potential conditions are particularly important if separation is required.

Figures 9.10 and 11 show configurations similar to those of Figures 6.7 and 8, respectively. It shows. Nine! In each configuration, both chambers 12A and 12B are magnetic are similarly aligned with respect to the field. Therefore, 1 each form of anger is M6.7 and 8 figures. The corresponding configuration in each of these also requires a powerful rotary actuator. shall be. In fact, a single fraction is comparable to either separator 56A or 56B! ! Requires twice the power for the device. The configuration of Figure 11 also allows for the required In addition to the rolling force, the actuator provides a substantial linear driving force along the common axis 13. Requires eta.

In each of the embodiments of FIGS. 9 and 10, the separators 56 and 56B are as shown in FIG. It should be operated independently to enjoy the benefits of the description and the form shown in Figure 7. cormorant.

However, the latter yields better throughput, while Fig. 9 and In the configuration of FIG. 10, the outlet 16B is bordered by the port 14A to provide two separators. When operated in series, a single sample is sampled for two chambers 12A and 12B. , complex filtering that allows arbitrary combinations of matrix and magnetization properties to be selected individually. receive. Thus, for example, detail #8 according to the format or the same format Additional protean properties can be obtained, such as sorting according to some useful differentiating characteristic. Ru. Instead, these configurations are such that chamber 12's mouths 14A and 16A are connected to chamber 12B's mouths. If connected to corresponding ports and the two chambers contain equal filtering properties, the unit operating A large processing volume can be provided per cycle.

The configuration shown in Figure 11 can easily accommodate 12 people in one room or 12 people in one room than the configuration in Figure 8. can be designed to permit repeated, sequential use of only If the 1 exit 16B in state? : Connected to the entrance for 14 people and has a low matrix in room 12B. 56 separators and s6B*i row using It is advantageous to provide a mechanical preheater for the magnetic filtering done at Ru.

FIG. 13 shows two separators 60 and 60, each having the same type as separator 10, for example. 62 shows a top view of another embodiment of the invention comprising 62; two horseshoes or C Shape permanent magnets 66 and 68 provide the magnetic fields used with separators 60 and 62. configured to do so. This arrangement is particularly easy to implement with readily available magnets. be. Each of the C-shaped magnets can also be covered with a sequential array of separate magnets.

At this time, if necessary, place another seven-parameter or magnetic flux coupler between the magnets that are in momentary contact. can do. Furthermore, in the exemplary form of this embodiment, a single separation device Either the minute M device 60 or 62 can be used to establish a high transparency f! is member It can be replaced. In other embodiments, separators 60 and 62 each , for example, as shown in Figures 86 to 12, a double separator may be used, but in this case, if necessary, If so, another set of magnets is added.

The present invention may be embodied in other specific forms without departing from its technical spirit. . It will be disclosed in the Book of Burmese! ljm Examples are intended to be illustrative and not restrictive. This invention is limited only by the scope of the following considerations. It is.

FIG.4 international search report

Claims (19)

[Claims] (1) In an apparatus for separating magnetic particles from a fluid medium, at least one inlet and at least one outlet extending along a first reference axis to direct fluid to the inlet; a first flow chamber that allows flow to flow from one of the outlets to one of the outlets; The flow of fluid in the matrix substantially passes through the pores in the matrix. a first high magnetic permeability fine-porous separation matrix disposed within the chamber; first magnetizing means for selectively coupling magnetic flux to the matrix; , wherein the first magnetizing means is arranged outside the chamber and on both sides of the first reference line. It has two magnetic poles of opposite polarity, The flow chamber includes a relatively high permeability member outside the matrix, and the first selectively rotatable about the first axis between a position and a second position; When the material is in the first position, the matrix is removed from one magnetic pole of the first magnetizing means. A first magnetic flux path is set through the magnetic pole to the other magnetic pole, When the member is in the second position, a comparative A second magnetic flux path of low magnetic reluctance extends from the one magnetic pole of the first magnetizing means to the other magnetic pole. set to the magnetic pole of A separation device characterized by: (2) comprising the first separation device and the second separation device, the second separation device comprising: at least one inlet and at least one outlet along the second reference axis; a second flow extending and causing fluid to flow from one of said inlets to one of said outlets; Fluid flow between the chamber, the entry inlet and the outlet a second high magnetic permeability fine-gap portion disposed within the second flow chamber so as to pass substantially through the gap; a separation matrix; second magnetizing means for selectively coupling magnetic flux to said matrix; , the second magnetizing means is located outside the second flow chamber and on both sides of the second reference axis. With two oppositely polarized magnetic poles placed on the side, The second flow chamber includes a relatively high magnetic permeability member outside the second matrix. , selectively rotatable about the second reference axis between a first position and a second position; When the member is in the first position, one magnetic pole of the second magnetizing means A first magnetic flux path passing through the two matrices and reaching the other magnetic pole is set, substantially external to the second matrix when the member is in the second position; A second magnet with low magnetic resistance extending from the one magnetic pole to the other magnetic pole of the second magnetizing means. A magnetic flux path is set, the first and second reference axes are coaxial with a common axis; 2. Separation device according to claim 1, wherein the second flow chamber is rigidly connected. (3) The magnetic pole of the first magnetizing means is arranged along the first polar axis, and the magnetic pole of the first magnetizing means is arranged along the first polar axis, and The magnetic pole of the converting means is arranged along a second polar axis, and the first polar axis is aligned with the second polar axis. parallel to the axis, and the second flow chamber is associated with the recording magnetic pole of the second magnetization means. and when in its second position, the first flow chamber is aligned with the magnetic pole of the first magnetizing means. the second flow chamber is in its first position with respect to the magnetic pole of the second magnetizing means; when the first flow chamber is in its first position with respect to the magnetic pole of the first magnetizing means. said first and second flow chambers are mutually oriented such that said first and second flow chambers are in their second position relative to each other; The separation device according to claim 2. (4) The magnetic pole of the first magnetizing means is arranged along the first polar axis, and the second magnetic pole The magnetic poles of the converting means are arranged along a second polar axis, and the first polar axis is aligned with the second polar axis. and the second flow chamber is parallel to the magnetic pole of the second magnetizing means. When in its first position, said first flow chamber is associated with said magnetic pole of said first magnetizing means. and the second flow chamber is in its first position relative to the magnetic pole of the second magnetizing means. when the first flow chamber is in its second position, the first flow chamber is connected to the magnetic pole of the first magnetizing means. the first and second flow chambers are oriented relative to each other such that the first and second flow chambers are in a second position relative to each other; The separation device according to claim 2. (5) The magnetic pole of the first magnetizing means is arranged along the first polar axis, and the magnetic pole of the first magnetizing means is arranged along the first polar axis, and The magnetic pole of the converting means is arranged along a second polar axis, and the first polar axis is aligned with the second polar axis. perpendicular to the axis, and the second flow chamber is associated with the magnetic pole of the second magnetizing means. and when in its second position, the first flow chamber is aligned with the magnetic pole of the first magnetizing means. The second flow chamber is in the first rank with respect to the magnetic pole of the second magnetizing means. when the first flow chamber is in its first position with respect to the magnetic pole of the first magnetizing means. said first and second flow chambers are mutually oriented such that said first and second flow chambers are in their second position relative to each other; The separation device according to claim 2. (6) The magnetic pole of the first magnetizing means is arranged along the first polar axis, and the magnetic pole of the first magnetizing means is arranged along the first polar axis, and The magnetic pole of the converting means is arranged along a second polar axis, and the first polar axis is aligned with the second polar axis. perpendicular to the line, and said second flow chamber is perpendicular to said magnetic pole of said second magnetizing means. When in its first position, said first flow chamber is associated with said magnetic pole of said first magnetizing means. and the second flow chamber is in its first position relative to the magnetic pole of the second magnetizing means. when the first flow chamber is in its second position, the first flow chamber is connected to the magnetic pole of the first magnetizing means. the first and second flow chambers are oriented relative to each other such that the first and second flow chambers are in a second position relative to each other; The separation device according to claim 2. (7) said first and second separating devices are movable between two positions along said common axis; said first and second magnetizing means are adapted to be movable, said first and second magnetizing means comprising magnetic poles of opposite polarity, and when the separating device is in one of the positions, the magnetic flux is coupled substantially to one of said flow chambers, and when said separation device is in the other of said positions, said the common pair of magnetic poles configured to substantially couple magnetic flux to the other of the flow chambers; 2. A separation device according to claim 2. (8) when the second flow chamber is in its second position with respect to the common pair of magnetic poles; , the first flow chamber is in its first position with respect to the common pair of magnetic poles; when the second flow chamber is in its first position with respect to the common pair of magnetic poles; said first orifice such that the flow chamber is in its second position with respect to said common pair of magnetic poles; 8. Separation device according to claim 7, wherein the and second flow chambers are mutually oriented. (9) the second flow chamber is in its first position with respect to the common pair of magnetic poles; the first flow chamber is in its first position with respect to the common pair of magnetic poles; When the two flow chamber is in its second position with respect to the common pair of magnetic poles, the first flow said first orifice such that the motion chamber is in its second position with respect to said common pair of magnetic poles; 8. Separation device according to claim 7, wherein the and second flow chambers are mutually oriented. (10) The one outlet of the first flow chamber is connected to the one inlet of the second flow chamber. 5. A separation device according to claim 4, which is coupled to a mouth. (11) The one outlet of the first flow chamber is connected to the one outlet of the second flow chamber. 7. A separation device according to claim 6, which is coupled to an inlet. (12) Claim 1, wherein said one inlet is at a lower level than said one outlet. Separation device as described. (13) the flow chamber and the matrix direct the fluid along a local vertical axis; so as to allow the fluid to flow through approximately along the fluid flow axis inclined in the range of 0 to 90° with respect to 2. Separation device according to claim 1, adapted to: (14) The separation device of claim 13, wherein said inclination is approximately equal to 45 degrees. (15) disposed within the flow chamber, and in the flow chamber, the matrix is a piezoelectric transducer in communication with the selectively driving the transducer to set up an acoustic wave within the flow chamber; 2. Separation device according to claim 1, further comprising operable excitation means. (16) The transducer is mechanically coupled to the matrix. Separation device according to scope 15. (17) The transducer is spaced apart from the matrix. 16. Separation device according to item 15. (18) The magnetizing means is arranged such that the N pole of each magnet is positioned opposite to the S pole of each magnet. The magnet consists of a pair of C-shaped permanent magnets, and the flow chamber is positioned opposite to the above. disposed between a pair of north and south poles, and further includes a pair of north and south poles disposed oppositely; The present invention further includes means for coupling magnetic flux between another set of the N and S poles. The separation device according to item 1. (19) The magnetic resistance path of the first magnetic flux path is relatively small compared to the magnetic resistance of the second magnetic flux path. Separation device according to claim 1.